title: Macrophages and recently identified forms of cell death.
abstract: Recent advances in cell death biology have uncovered an ever increasing range of cell death forms. Macrophages have a bidirectional relationship with cell death that modulates the immune response. Thus, macrophages engulf apoptotic cells and secrete cytokines that may promote cell death in parenchymal cells. Furthermore, the presence of apoptotic or necrotic dead cells in the microenvironment elicits differential macrophage responses. Apoptotic cells elicit anti-inflammatory responses in macrophages. By contrast macrophages may undergo a proinflammatory form of cell death (pyroptosis) in response to damage-associated molecular patterns (DAMPs) released from necrotic cells and also in response to pathogen-associated molecular patterns (PAMPs). Pyroptosis is a recently identified form of cell death that occurs predominantly in subsets of inflammatory macrophages and is associated to the release of interleukin-1β (IL-1β) and IL-18. Deregulation of these processes may result in disease. Thus, failure of macrophages to engulf apoptotic cells may be a source of autoantigens in autoimmune diseases, excessive macrophage release of proapoptotic factors or sterile pyroptosis may contribute to tissue injury and failure of pathogen-induced pyroptosis may contribute to pathogen survival. Ongoing research is exploring the therapeutic opportunities resulting this new knowledge.
authors.affiliation: 1Laboratory of Nephrology, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Sanz
authors.forename: Maria D
authors.initials: MD
authors.lastname: Sanchez-Niño
authors.forename: Maria C
authors.initials: MC
authors.lastname: Izquierdo
authors.forename: Liliana
authors.initials: L
authors.lastname: Gonzalez-Espinoza
authors.forename: Alvaro C
authors.initials: AC
authors.lastname: Ucero
authors.forename: Jonay
authors.initials: J
authors.lastname: Poveda
authors.forename: Olga
authors.initials: O
authors.lastname: Ruiz-Andres
authors.forename: Marta
authors.initials: M
authors.lastname: Ruiz-Ortega
authors.forename: Rafael
authors.initials: R
authors.lastname: Selgas
authors.forename: Jesus
authors.initials: J
authors.lastname: Egido
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
mesh_terms: D000818:Animals; D017209:Apoptosis; D016923:Cell Death / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D009336:Necrosis